This proposal combines psychophysical techniques and functional magnetic resonance imaging (fMRI) to Study how physiological significance, individual differences and acute stress influence neural response to the ingestion of tastes and flavors in healthy human subjects. The work is guided by the view that there are distinct subsystems representing nutritive vs. harmful oral stimuli, and that individual factors, such as taste preference and genetics, as well as environmental factors, such as stress, influences how the nutritive subsystem responds to the ingestion of caloric substances. Relatively little is known about how the human brain encodes food. The overarching goal ofthis work is to further the understanding of the basic organization of oral sensation and then to determine how the system is influenced by Individual and environmental factors. Aim 1 ofthis proposal is a work in progress. I used fMRI to test the hypothesis that oral stimuli (taste and chemesthetic) of like physiological significance produce overlapping responses that are distinct from oral stimuli of opposite physiological significance. Preliminary findings support the prediction and show greater connectivity between the insula and hypo- thalamus during sensation ofa nutritive vs. a harmful oral sensation. In Aim 2, I propose to test how individual differences in sweet concentration preference Influence brain response to sweet taste and to determine whether differential responses predict future weight gain. Finally, in Aim 3 I will test the hypo- thesis that an acute stressor will cause brain response to a milkshake drink to more closely resemble that of obese subjects, and that the extent of the Influence of stress predicts weight gain at one-year follow-up. The data resulting from this proposal will provide fundamental Information on sensory encoding of food and help to Identify potential biomarkers for weight gain susceptibility. PUBLIC HEALTH RELEVANCE: The rapid onset of the obesity epidemic has necessitated a shift In focus from metabolic factors towards consideration of Individual factors, such as taste preference, which may interact with environmental factors such as the availability of energy dense foods or increased stress, whose increasing presence In modern society closely tracks the incidence of obesity. The proposed studies will provide fundamental information about how sweet taste preference and acute stress Influence brain response to palatable and calorically dense flavors. Moreover, this work will determine If brain regions that respond differentially as a function of preference or stress influence future weight gain, thus potentially leading to the identification of biomarkers for weight gain susceptibility.